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Glioblastoma Myeloid-Derived Suppressor Cell Subsets Express Differential Macrophage Migration Inhibitory Factor Receptor Profiles That Can Be Targeted to Reduce Immune Suppression
The application of tumor immunotherapy to glioblastoma (GBM) is limited by an unprecedented degree of immune suppression due to factors that include high numbers of immune suppressive myeloid cells, the blood brain barrier, and T cell sequestration to the bone marrow. We previously identified an inc...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315581/ https://www.ncbi.nlm.nih.gov/pubmed/32625208 http://dx.doi.org/10.3389/fimmu.2020.01191 |
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author | Alban, Tyler J. Bayik, Defne Otvos, Balint Rabljenovic, Anja Leng, Lin Jia-Shiun, Leu Roversi, Gustavo Lauko, Adam Momin, Arbaz A. Mohammadi, Alireza M. Peereboom, David M. Ahluwalia, Manmeet S. Matsuda, Kazuko Yun, Kyuson Bucala, Richard Vogelbaum, Michael A. Lathia, Justin D. |
author_facet | Alban, Tyler J. Bayik, Defne Otvos, Balint Rabljenovic, Anja Leng, Lin Jia-Shiun, Leu Roversi, Gustavo Lauko, Adam Momin, Arbaz A. Mohammadi, Alireza M. Peereboom, David M. Ahluwalia, Manmeet S. Matsuda, Kazuko Yun, Kyuson Bucala, Richard Vogelbaum, Michael A. Lathia, Justin D. |
author_sort | Alban, Tyler J. |
collection | PubMed |
description | The application of tumor immunotherapy to glioblastoma (GBM) is limited by an unprecedented degree of immune suppression due to factors that include high numbers of immune suppressive myeloid cells, the blood brain barrier, and T cell sequestration to the bone marrow. We previously identified an increase in immune suppressive myeloid-derived suppressor cells (MDSCs) in GBM patients, which correlated with poor prognosis and was dependent on macrophage migration inhibitory factor (MIF). Here we examine the MIF signaling axis in detail in murine MDSC models, GBM-educated MDSCs and human GBM. We found that the monocytic subset of MDSCs (M-MDSCs) expressed high levels of the MIF cognate receptor CD74 and was localized in the tumor microenvironment. In contrast, granulocytic MDSCs (G-MDSCs) expressed high levels of the MIF non-cognate receptor CXCR2 and showed minimal accumulation in the tumor microenvironment. Furthermore, targeting M-MDSCs with Ibudilast, a brain penetrant MIF-CD74 interaction inhibitor, reduced MDSC function and enhanced CD8 T cell activity in the tumor microenvironment. These findings demonstrate the MDSC subsets differentially express MIF receptors and may be leveraged for specific MDSC targeting. |
format | Online Article Text |
id | pubmed-7315581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73155812020-07-02 Glioblastoma Myeloid-Derived Suppressor Cell Subsets Express Differential Macrophage Migration Inhibitory Factor Receptor Profiles That Can Be Targeted to Reduce Immune Suppression Alban, Tyler J. Bayik, Defne Otvos, Balint Rabljenovic, Anja Leng, Lin Jia-Shiun, Leu Roversi, Gustavo Lauko, Adam Momin, Arbaz A. Mohammadi, Alireza M. Peereboom, David M. Ahluwalia, Manmeet S. Matsuda, Kazuko Yun, Kyuson Bucala, Richard Vogelbaum, Michael A. Lathia, Justin D. Front Immunol Immunology The application of tumor immunotherapy to glioblastoma (GBM) is limited by an unprecedented degree of immune suppression due to factors that include high numbers of immune suppressive myeloid cells, the blood brain barrier, and T cell sequestration to the bone marrow. We previously identified an increase in immune suppressive myeloid-derived suppressor cells (MDSCs) in GBM patients, which correlated with poor prognosis and was dependent on macrophage migration inhibitory factor (MIF). Here we examine the MIF signaling axis in detail in murine MDSC models, GBM-educated MDSCs and human GBM. We found that the monocytic subset of MDSCs (M-MDSCs) expressed high levels of the MIF cognate receptor CD74 and was localized in the tumor microenvironment. In contrast, granulocytic MDSCs (G-MDSCs) expressed high levels of the MIF non-cognate receptor CXCR2 and showed minimal accumulation in the tumor microenvironment. Furthermore, targeting M-MDSCs with Ibudilast, a brain penetrant MIF-CD74 interaction inhibitor, reduced MDSC function and enhanced CD8 T cell activity in the tumor microenvironment. These findings demonstrate the MDSC subsets differentially express MIF receptors and may be leveraged for specific MDSC targeting. Frontiers Media S.A. 2020-06-18 /pmc/articles/PMC7315581/ /pubmed/32625208 http://dx.doi.org/10.3389/fimmu.2020.01191 Text en Copyright © 2020 Alban, Bayik, Otvos, Rabljenovic, Leng, Jia-Shiun, Roversi, Lauko, Momin, Mohammadi, Peereboom, Ahluwalia, Matsuda, Yun, Bucala, Vogelbaum and Lathia. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Alban, Tyler J. Bayik, Defne Otvos, Balint Rabljenovic, Anja Leng, Lin Jia-Shiun, Leu Roversi, Gustavo Lauko, Adam Momin, Arbaz A. Mohammadi, Alireza M. Peereboom, David M. Ahluwalia, Manmeet S. Matsuda, Kazuko Yun, Kyuson Bucala, Richard Vogelbaum, Michael A. Lathia, Justin D. Glioblastoma Myeloid-Derived Suppressor Cell Subsets Express Differential Macrophage Migration Inhibitory Factor Receptor Profiles That Can Be Targeted to Reduce Immune Suppression |
title | Glioblastoma Myeloid-Derived Suppressor Cell Subsets Express Differential Macrophage Migration Inhibitory Factor Receptor Profiles That Can Be Targeted to Reduce Immune Suppression |
title_full | Glioblastoma Myeloid-Derived Suppressor Cell Subsets Express Differential Macrophage Migration Inhibitory Factor Receptor Profiles That Can Be Targeted to Reduce Immune Suppression |
title_fullStr | Glioblastoma Myeloid-Derived Suppressor Cell Subsets Express Differential Macrophage Migration Inhibitory Factor Receptor Profiles That Can Be Targeted to Reduce Immune Suppression |
title_full_unstemmed | Glioblastoma Myeloid-Derived Suppressor Cell Subsets Express Differential Macrophage Migration Inhibitory Factor Receptor Profiles That Can Be Targeted to Reduce Immune Suppression |
title_short | Glioblastoma Myeloid-Derived Suppressor Cell Subsets Express Differential Macrophage Migration Inhibitory Factor Receptor Profiles That Can Be Targeted to Reduce Immune Suppression |
title_sort | glioblastoma myeloid-derived suppressor cell subsets express differential macrophage migration inhibitory factor receptor profiles that can be targeted to reduce immune suppression |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315581/ https://www.ncbi.nlm.nih.gov/pubmed/32625208 http://dx.doi.org/10.3389/fimmu.2020.01191 |
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